M-4312-C-T

Variant names:

• chrM-4312-C-T
• rs193303033
• unassigned_transcript_4790:c.50C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000000000(TRNI):​c.50C>T​(p.Ala17Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. 3/3 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.028 (AC: 1683)
• Consequence: TRNI ENST00000000000 missense
• Scores: Mitotip Benign 3.5
• Clinical Significance: Benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 2.50
• Publications: 3 publications found

Genes affected

TRNI (HGNC:7488): (mitochondrially encoded tRNA isoleucine)

MT-ND2 (HGNC:7456): (mitochondrially encoded NADH dehydrogenase 2) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Part of mitochondrial respiratory chain complex I. Implicated in Leber hereditary optic neuropathy; multiple sclerosis; myocardial infarction; neurodegenerative disease (multiple); and urinary bladder cancer. [provided by Alliance of Genome Resources, Apr 2022]

MT-ND1 (HGNC:7455): (mitochondrially encoded NADH dehydrogenase 1) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Located in mitochondrial membrane. Part of mitochondrial respiratory chain complex I. Implicated in several diseases, including MELAS syndrome; neurodegenerative disease (multiple); optic nerve disease (multiple); toxic shock syndrome; and type 2 diabetes mellitus. Biomarker of Alzheimer's disease; Parkinson's disease; and multiple sclerosis. [provided by Alliance of Genome Resources, Apr 2022]

TRNM (HGNC:7492): (mitochondrially encoded tRNA methionine)

TRNQ (HGNC:7495): (mitochondrially encoded tRNA glutamine)

TRNQ Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant M-4312-C-T is Benign according to our data. Variant chrM-4312-C-T is described in ClinVar as Benign. ClinVar VariationId is 689877.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: High frequency in mitomap database: 0.0275

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000387365.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT-TI	ENST00000387365.1	TSL:6	n.50C>T		non_coding_transcript_exon	Exon 1 of 1
	MT-ND2	ENST00000361453.3	TSL:6	c.-158C>T		upstream_gene	N/A	ENSP00000355046.4	P03891
	MT-ND1	ENST00000361390.2	TSL:6	c.*50C>T		downstream_gene	N/A	ENSP00000354687.2	P03886

Frequencies

Mitomap GenBank AF: 0.028 AC: 1683

Gnomad homoplasmic AF: 0.012 AC: 663 AN: 56418

Gnomad heteroplasmic AF: 0.000035 AC: 2 AN: 56418

Alfa AF: 0.00859 Hom.: 398

Mitomap

No disease associated.

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	MELAS syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Mitotip	Benign	3.5
Hmtvar	Benign	0.30
PhyloP100		2.5

Other links and lift over

dbSNP: rs193303033; hg19: chrM-4313;